Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites.
Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites.
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DOI：
10.1073/pnas.1810053115
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发表时间：
2018-09-04
影响因子：
11.1
通讯作者：
Hahn BH
中科院分区：
文献类型：
--
作者：
Loy DE;Plenderleith LJ;Sundararaman SA;Liu W;Gruszczyk J;Chen YJ;Trimboli S;Learn GH;MacLean OA;Morgan ALK;Li Y;Avitto AN;Giles J;Calvignac-Spencer S;Sachse A;Leendertz FH;Speede S;Ayouba A;Peeters M;Rayner JC;Tham WH;Sharp PM;Hahn BH
黑猩猩、倭黑猩猩和大猩猩都有人类间日疟原虫的近亲，但目前对这些寄生虫的了解仅限于少数几乎完全来自线粒体DNA的基因片段。我们将猿类寄生虫的几乎全长基因组与全球人类间日疟原虫样本进行了比较，并测试了人类和猿类间日疟原虫蛋白质的功能，这些蛋白质被认为对红细胞结合很重要。结果表明，猿类寄生虫的多样性是人类间日疟原虫的10倍，并且没有表现出物种特异性的证据，而人类间日疟原虫代表了从该寄生虫群中出现的一个单克隆谱系。因此，非洲猿是间日疟原虫的一个大宿主，其对人类疟疾根除的影响需要仔细监测。野生的非洲猿感染了与人类间日疟原虫密切相关的寄生虫，这是非洲以外疟疾的主要原因。这一发现表明间日疟原虫的起源是在非洲，尽管这种寄生虫现在在那里的人类中很少见。为了阐明人类间日疟原虫的出现及其与猿类寄生虫的关系，我们分析了感染喀麦隆、加蓬和科特迪瓦6只黑猩猩和1只大猩猩的间日疟原虫菌株的基因组序列数据。我们发现猿类和人类寄生虫拥有几乎相同的核心基因组，编码序列仅相差2%。然而，与猿类寄生虫相比，间日疟原虫的人类菌株表现出约10倍的多样性，并具有相对过量的非同义核苷酸多态性，位点频谱表明它们受到非常宽松的纯化选择。这些数据表明，人类间日疟原虫已经经历了一个极端的瓶颈，随后是人口的快速增长。研究潜在的宿主特异性决定因素，我们发现猿间日疟原虫寄生虫编码三个网织红细胞结合蛋白基因（rbp2d，rbp2e和rbp3）的完整直系同源物，这些基因在所有人类间日疟原虫菌株中都是假基因。然而，重组RBP2e和RBP3蛋白与人类，黑猩猩和大猩猩红细胞的结合研究显示，没有证据表明宿主特异性屏障红细胞入侵。这些数据表明，从能够感染人类和猿类的间日疟原虫古老种群中，非洲出现了一个严重瓶颈的谱系，并在全球传播过程中经历了快速的人口增长。
Chimpanzees, bonobos, and gorillas harbor close relatives of human Plasmodium vivax, but current knowledge of these parasites is limited to a small number of gene fragments derived almost exclusively from mitochondrial DNA. We compared nearly full-length genomes of ape parasites with a global sample of human P. vivax and tested the function of human and ape P. vivax proteins believed to be important for erythrocyte binding. The results showed that ape parasites are 10-fold more diverse than human P. vivax and exhibit no evidence of species specificity, whereas human P. vivax represents a bottlenecked lineage that emerged from within this parasite group. Thus, African apes represent a large P. vivax reservoir whose impact on human malaria eradication requires careful monitoring. Wild-living African apes are endemically infected with parasites that are closely related to human Plasmodium vivax, a leading cause of malaria outside Africa. This finding suggests that the origin of P. vivax was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human P. vivax and its relationship to the ape parasites, we analyzed genome sequence data of P. vivax strains infecting six chimpanzees and one gorilla from Cameroon, Gabon, and Côte d’Ivoire. We found that ape and human parasites share nearly identical core genomes, differing by only 2% of coding sequences. However, compared with the ape parasites, human strains of P. vivax exhibit about 10-fold less diversity and have a relative excess of nonsynonymous nucleotide polymorphisms, with site-frequency spectra suggesting they are subject to greatly relaxed purifying selection. These data suggest that human P. vivax has undergone an extreme bottleneck, followed by rapid population expansion. Investigating potential host-specificity determinants, we found that ape P. vivax parasites encode intact orthologs of three reticulocyte-binding protein genes (rbp2d, rbp2e, and rbp3), which are pseudogenes in all human P. vivax strains. However, binding studies of recombinant RBP2e and RBP3 proteins to human, chimpanzee, and gorilla erythrocytes revealed no evidence of host-specific barriers to red blood cell invasion. These data suggest that, from an ancient stock of P. vivax parasites capable of infecting both humans and apes, a severely bottlenecked lineage emerged out of Africa and underwent rapid population growth as it spread globally.
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影响因子：
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